Halogen Bond Motifs in Cocrystals of N, N, O and N, O, O Acceptors Derived from Diketones and Containing a Morpholine or Piperazine Moiety

Ruđer Sušanj; Vinko Nemec; Nikola Bedeković; Dominik Cinčić

doi:10.1021/acs.cgd.2c00665

Halogen Bond Motifs in Cocrystals of N, N, O and N, O, O Acceptors Derived from Diketones and Containing a Morpholine or Piperazine Moiety

Cryst Growth Des. 2022 Sep 7;22(9):5135-5142. doi: 10.1021/acs.cgd.2c00665. Epub 2022 Aug 1.

Authors

Ruđer Sušanj¹, Vinko Nemec¹, Nikola Bedeković¹, Dominik Cinčić¹

Affiliation

¹ Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia.

Abstract

In this study, we investigate the halogen bond acceptor potential of oxygen and nitrogen atoms of morpholine and piperazine fragments when they are peripherally located on N,O,O or N,N,O acceptor molecules. We synthesized four acceptor molecules derived from either acetylacetone or benzoylacetone and cocrystallized them with 1,4-diiodotetrafluorobenzene and 1,3,5-triiodotrifluorobenzene. This resulted in eight cocrystals featuring different topicities and geometric dispositions of donor atoms. In all cocrystals, halogen bonds are formed with either the morpholinyl oxygen atom or the terminal piperazine nitrogen atom. The I···O_morpholine halogen bonds feature lower relative shortening values than I···N_terminal, I···O_carbonyl, and I···N_proximal halogen bonds. The N and O halogen bond acceptor sites were evaluated through calculations of molecular electrostatic potential values.